Toxicon 2025 Mar 29;256:108264. doi: 10.1016/j.toxicon.2025.108264.

Capsaicin preferentially inhibits slow-inactivation sodium currents in insects.

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Capsaicin, a pungent ingredient found in chili peppers, exhibits various pharmacological activities including inhibiting voltage-gated sodium channels (VGSCs) in mammals, suppressing sodium currents. Although capsaicin shows insecticidal activity, its underlying mechanism of action on insect VGSCs remains unclear. Here, we evaluated the effects of capsaicin on insect nerve cords and VGSCs using neurophysiological techniques. Capsaicin injection immediately induced paralysis in American cockroaches (Periplaneta americana). Extracellular recordings of their nerve cords revealed that capsaicin inhibited the allethrin-induced excitation of nerve cord activity. Furthermore, in Xenopus oocytes expressing VGSCs of German cockroaches (Blattella germanica), capsaicin inhibited the steady-state activation of VGSCs, with an IC50 value of 130.6 μM. Capsaicin significantly shifted the half-inactivation potential of the inactivation curve of insect VGSCs in a slow-inactivated state from -44.61 to -48.92 mV. Although the state dependency of sodium current inhibition by capsaicin remains unknown, based on its effective concentration, capsaicin may preferentially inhibit sodium currents by acting on insect VGSCs in a slow-inactivated state. This unique profile may serve as a foundation for the creation of novel insecticides based on capsaicin properties.

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